Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002601855 | SCV002956931 | pathogenic | Cholestanol storage disease | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 7 of the CYP27A1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.007%). Disruption of this splice site has been observed in individuals with cerebrotendinous xanthomatosis (PMID: 8827518, 26622071, 27878435). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1918228). Studies have shown that disruption of this splice site results in skipping of exon 7 and introduces a premature termination codon (PMID: 8827518). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |